Many aspects of development require the migration of individual cells through diverse and complex environments. In vertebrate embryos, for example, neural crest cells leave the developing central nervous system and migrate over long distances to give rise to such cell types as sensory neurons, facial cartilage and pigment cells of the skin. In adults, migratory cell types include the cells of the immune system, fibroblasts during wound healing, and cancer cells during metastasis. During directed cell migration, motile cells are guided along a particular path, they recognize guidance cues and translate them into directed movement. Primordial germ cells (PGCs) provide an excellent model system for the analysis of directed cell migration. Many aspects of germ cell biology, such as their overall morphology and their curious migratory path toward the somatic components of the gonad are conserved throughout the animal kingdom. Repulsion from the posterior midgut and attraction toward the somatic gonadal precursors orients germ cells during their migration in Drosophila. An attractant guidance cue is provided by Drosophila HMGCoA reductase. High levels of HMGCoA reductase are both necessary and sufficient to attract PGCs to the somatic gonad. A repellant guidance cue is provided by two redundantly acting proteins, Wunen and Wunen 2, which are expressed on the midgut. Ectopic Wunen/Wunen 2 expression repels germ cells and at high levels leads to PGC death. This study proposes to characterize these repellant and attractive signaling systems and to determine the nature of the respective signals using genetic and biochemical techniques. This study further aims to determine the molecular nature of receptors in the germ cells that mediate the migratory response. Given the conservation of developmental mechanisms among animals it is likely that studies on the molecular mechanisms of germ cells guidance will contribute to the analysis of germ cell migration in general.